Superficial (skin, hair, and nail) fungal and bacterial infections are estimated to affect over 1 billion people worldwide and 27 million people in the US. Superficial fungal infection of the skin and nails is common and is on the rise due to an aging population, the increasing prevalence of diabetes, and the widespread use of antifungals and antibiotics in medicine and in the environment. In diabetics and the immunosuppressed, onychomycosis is a risk factor for serious infections, such as cellulitis and foot ulcers. For some, however, nail infection is simply a cosmetic issue.
Fungal infection of the nail, known as onychomycosis, is a common and difficult to treat condition, most frequently affecting the toes. Dermatophyte molds (e.g., Trichophyton rubrum) cause the majority of infected nails, followed by yeasts, such as Candida albicans, and the non-dermatophyte molds, such as aspergillus. Infection usually starts in the skin, (so-called “athlete's foot”), and then spreads to the nail unit after trauma breaks the seal between the nail plate and the nail bed, allowing fungi to penetrate the nail. Fungi are typically found in the nail plate itself and below the nail plate in the nail bed.
Commercially available treatments include systemic administration of antifungal compounds such as griseofulvin, ketoconazole, itraconazole, fluconazole, and terbinafine. Systemic therapies, while more effective, carry the risk of serious side effects including liver failure, severe allergic reactions, as well as drug interactions. Furthermore, systemic therapies often require long-term treatment courses and laboratory monitoring.
Topical application of an antifungal drug is an attractive alternative to systemic administration. However, most topical antifungal formulations (e.g., clotrimazole, terbinafine) are totally ineffective for onychomycosis because they do not penetrate the nail, likely due to their high molecular weight. There are two topical antibiotics currently being marketed for onychomycosis: ciclopirox and amorolfin. Unfortunately, however, they not been very effective with cure rates in the 5-30% range. Thus, there is a need for an effective, safe, and convenient treatment for onychomycosis.
Halogen-based compounds have been used for treatment of infections including onychomycosis. Halogen based formulations readily penetrate the nail because of their small molecular weight. However, currently available halogen solutions (e.g., Dakin's solution) are unstable once applied to the nail, limiting their use. Furthermore, efficacy and side effects of topically applied halogen based solutions have not been well studied in the clinical setting. Sodium hypochlorite, available commonly as bleach, is a known skin irritant. Furthermore, it is well known that the chlorine, chlorine dioxide, and hypochlorous acid decompose readily upon exposure to light and air. The use of a chlorine dioxide solution as an antimicrobial agent is described in WO 2006/088790. In this study, subjects were required to soak the whole foot in a large volume of freshly made chlorine dioxide solution while in a darkened room. Aside from the inconvenience, the normal skin and nails are unnecessarily exposed to chlorine dioxide potentially causing irritation. Furthermore, high concentrations of chorine dioxide can constitute an explosive hazard.
Despite the advances in the treatment of infections, particularly skin and skin appendage infections, a need exists for a simple and effective treatment that do not suffer from the disadvantages noted above. The present invention seeks to fulfill this need and provides further related advantages.